ARV-393 / Arvinas - LARVOL DELTA

Arvinas to Present Preclinical Data for PROTAC BCL6 Degrader, ARV-393, at 2025 American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "Arvinas, Inc...today announced that new preclinical combination data for ARV-393 will be presented at the American Association for Cancer Research (AACR) Annual meeting, April 25-30, 2025 in Chicago, Illinois. The poster highlights the potential for ARV-393 to be combined with various standard of care lymphoma treatments."

Preclinical • Diffuse Large B Cell Lymphoma

ARV-393, a PROTAC B-cell lymphoma 6 (BCL6) degrader, combined with biologics or small molecule inhibitors (SMIs) induces tumor regressions in diffuse large B-cell lymphoma (DLBCL) models (AACR 2025) - P1 | "For example, CREBBP/EP300 and BCL6 have opposing transcriptional activities and BCL6 degradation may prevent CD20 downregulation by restoring CREBBP/EP300 chromatin access, supporting combination with anti-CD20 biologics; cooperation of EZH2 with the BCL6 repressor complex supports combining with tazemetostat (taz). Thus, we assessed the activity of ARV-393 in combination with biologics or SMIs based on potential complementary mechanistic roles.ARV-393 was administered in combination with clinically relevant doses of the standard of care (SOC) biologics rituximab, tafasitamab (tafa) and polatuzumab to mice bearing SU-DHL-4 CDX, representing a high-grade B-cell lymphoma (HGBCL, with MYC, BCL2 and BCL6 rearrangements). ARV-393 was also combined with investigational SMIs of EZH2 (taz), BCL2 (venetoclax) and BTK (acalabrutinib), in HGBCL or aggressive CDX models SU-DHL-6 (EZH2mut), OCI-Ly1 (BCL2+) and activated B-cell (ABC)-like OCI-Ly10 (MYD88 mut),..."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Oncology • BCL2 • BCL6 • CREBBP • EP300 • MYC • MYD88

Arvinas Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "ARV-393: Oral PROTAC BCL6 degrader: Present preclinical data of ARV-393 in combination with standard of care biologic agents and small molecule inhibitors in high grade and aggressive diffuse large B-cell lymphoma in vivo models at the American Association for Cancer Research Annual Meeting (April 25-30, 2025). Disclose preliminary data from the ongoing Phase 1 clinical trial in patients with NHL (ClinicalTrials.gov Identifier: NCT06393738) in 2025....Novel PROTAC KRAS G12D degrader: File an Investigational New Drug (IND) application in 2025."

IND • P1 data • Preclinical • Diffuse Large B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Solid Tumor

Arvinas…Highlights Upcoming Milestones, and Provides Corporate Update (GlobeNewswire) - "ARV-393: Oral PROTAC BCL6 degrader - Present initial data from the ongoing Phase 1 clinical trial in patients with B-cell lymphomas (NCT06393738). Novel PROTAC KRAS G12D degrader: File an Investigational New Drug (IND) application."

IND • P1 data • Non-Hodgkin’s Lymphoma • Oncology

Phase 1 Study of ARV-393, a PROTAC BCL6 Degrader, in Advanced Non-Hodgkin Lymphoma (ASH 2024) - P1 | "Secondary objectives are to characterize the pharmacokinetic profile of ARV-393 and evaluate its preliminary antitumor activity. Enrollment is currently ongoing."

Metastases • P1 data • B Cell Lymphoma • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • High-grade B-cell lymphoma • Hypereosinophilic Syndrome • Immunology • Infectious Disease • Interstitial Lung Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Organ Transplantation • T Cell Non-Hodgkin Lymphoma • Targeted Protein Degradation • BCL6 • CRBN

Arvinas Reports Third Quarter 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "ARV-393: Oral PROTAC BCL6 degrader - Continue recruiting patients in the first-in-human Phase 1 clinical trial evaluating ARV-393 in patients with B-cell lymphomas. Novel PROTAC KRAS G12D degrader: File an Investigational New Drug (IND) application in 2025."

IND • Trial status • Non-Hodgkin’s Lymphoma

ARV-393-101: A Study of ARV-393 in Relapsed/Refractory Non-Hodgkin Lymphoma. (clinicaltrials.gov) - P1 | N=112 | Recruiting | Sponsor: Arvinas Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

ARV-393-101: A Study of ARV-393 in Relapsed/Refractory Non-Hodgkin Lymphoma. (clinicaltrials.gov) - P1 | N=112 | Not yet recruiting | Sponsor: Arvinas Inc. | Initiation date: Apr 2024 ➔ Aug 2024

Metastases • Trial initiation date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Arvinas Announces Presentations for Two of its PROTAC Investigational Programs Targeting BCL6 and LRRK2 (GlobeNewswire) - "Data presented at EHA showed anti-tumor activity for the company’s investigational PROTAC BCL6 degrader, ARV-393, in preclinical models of B-cell lymphoma. In these preclinical models, ARV-393 potently and rapidly degraded the BCL6 protein and inhibited cell growth in diffuse large B-cell lymphoma (DLBCL) and Burkitt cell lines. ARV-393 showed tumor growth inhibition, including tumor regression, in various DLBCL cell line-derived xenograft (CDX) models and in multiple patient-derived xenograft (PDX) models of non-Hodgkin lymphoma (NHL), including germinal center B-cell-like (GCB), activated B-cell (ABC), GCB/ABC, BCL not otherwise specified (BCL/NOS) subtypes of DLBCL, and Burkitt lymphoma."

Preclinical • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

ORAL ARV-393 IS A BCL6 DEGRADING PROTAC EFFICACIOUS AS MONOTHERAPY IN B-CELL LYMPHOMA PRECLINICAL CDX AND PDX MODELS (EHA 2024) - "ARV-393 is an oral PROTAC BCL6 degrader that demonstrated potent anti-tumormonotherapy activity in numerous preclinical models of NHL, indicating this molecule may provide a significanttherapeutic benefit to NHL patients."

IO biomarker • Monotherapy • Preclinical • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • Targeted Protein Degradation • BCL2 • BCL6 • CRBN

TRIAL IN PROGRESS: PHASE 1 STUDY OF ARV-393, A PROTAC BCL6 DEGRADER, IN ADVANCED NON-HODGKIN LYMPHOMA (EHA 2024) - "This will be the first clinical study of ARV-393, a potent, selective, oral PROTAC BCL6degrader, in patients with advanced relapsed/refractory NHL."

Metastases • P1 data • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Organ Transplantation • T Cell Non-Hodgkin Lymphoma • Targeted Protein Degradation • Transplantation • BCL6 • CRBN

Arvinas Reports First Quarter 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "Initiate discussion with regulatory authorities on a second-line Phase 3 trial of vepdegestrant in combination with palbociclib and potentially other CDK4/6 inhibitors, and a new first-line Phase 3 trial of vepdegestrant plus atirmociclib, Pfizer’s novel CDK4 inhibitor....Initiate dosing in first-in-human Phase 1 clinical trial in B-cell lymphomas with PROTAC BCL6 degrader ARV-393 (2Q 2024)....The decrease in research and development expenses of $11.0 million for the quarter was primarily due to a decrease in expenses related to our AR program (which includes ARV-766 and bavdegalutamide (ARV-110)) of $8.2 million, our ER program (which includes the cost sharing of vepdegestrant under the Vepdegestrant (ARV-471) Collaboration Agreement) of $2.3 million and our platform and exploratory programs of $0.5 million."

Commercial • Regulatory • Trial status • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of ARV-393 in Relapsed/Refractory Non-Hodgkin Lymphoma. (clinicaltrials.gov) - P1 | N=112 | Recruiting | Sponsor: Arvinas Inc.

Metastases • New P1 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

The discovery of ARV-393, a potent, orally bioavailable BCL6 targeting PROTAC® for the treatment of Non-Hodgkin's Lymphoma (AACR 2024) - "Despite the success of R-CHOP treatment, approximately 40% of patients are refractory or relapse. This agent demonstrates deep BCL6 degradation in vitro and in vivo, resulting in excellent TGI in several tumor xenograft models supporting a first-in-human trial in 1H 2024. We will present the chemical structure of ARV-393 and selected pre-clinical data."

Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL6 • CRBN

Arvinas Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "Initiate first-in-human Phase 1 clinical trial in B-cell lymphomas with BCL6 targeting PROTAC ARV-393 (1H 2024)....The increase in research and development expenses of $64.7 million for the year was primarily due to an increase in expenses associated with our platform and exploratory programs of $1.1 million, our AR program (which includes ARV-766 and bavdegalutamide (ARV-110)) of $22.0 million and our ER program of $41.6 million, which includes the cost sharing of vepdegestrant (ARV-471) under the Vepdegestrant (ARV-471) Collaboration Agreement."

Commercial • New P1 trial • Hematological Malignancies • Lymphoma • Oncology

Arvinas Reports Third Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "Submit two investigational new drug (IND)/clinical trial authorization (CTA) applications for the Company’s BCL6 (oncology)...Progress at least two additional PROTAC protein degrader programs into IND- or CTA-enabling studies by year-end 2023....The increase in research and development expenses of $8.4 million for the quarter was primarily due to increases our AR program of $5.2 million, which includes ARV-766 and bavdegalutamide, and our ER program of $6.2 million, which is net of the cost sharing of vepdegestrant under the Vepdegestrant (ARV-471) Collaboration Agreement, offset by a decrease in our platform and exploratory programs of $3.0 million."

Commercial • IND • Oncology